Prostaglandin E2 정의 경구투여법과 Oxytocin 정맥내 지속점적 주입법에 의한 유도분만의 비교관찰

김인규(IK Kim),박찬규(CK Park),송찬호(CH Song),임희규(HK Lim),민병열(BY Min),오기석(KS Oh) 대한산부인과학회 1978 Obstetrics & Gynecology Science Vol.21 No.12

1978년 3월부터 1978년 8월까지 연세대학교 의과대학, 부속 세브란스병원 산부인과에 유도분만을 목적으로 입원한 산모중 42예를 일정한 선택기준에 의하여 선정, 경구 prostaglandin E2 정제를 투여하여 유도분만을 시도하였으며 그 결과를 대조군인 oxytocin 정맥내 지속점적 주입군 120예의 분만효과와 비교관찰하여 다음과 같은 결론을 얻었다. 1) 성공율은 수정된 Bishops치 4이하에서 prostaglandin E2군이 59.1%, oxytocin군이 55.8%, 5~9치에서 prostaglandin E2군이 100.0%, oxytocin군이 91.3%, 10이상의 치에서는 두군 모두 100.0%이였다. 2) 평균 진통 및 분만 소요시간은 prostaglandin E2군이 초산부 12.78 3.8시간, 경산부 5.26 3.22시간이었고, oxytocin군은 초산부 12.47 1.9시간, 경산부 3.76 0.55시간이었다. 3) 경구 prostaglandin E2정의 평균 사용량은 2.46 0.4mg이었다. 4) 부작용으로는 prostaglandin E2군은 오심 및 구토가 4예(9.5%), 설사가 1예(2.4%), 이완성 자궁출혈이 2예(4.7%)였으며, oxytocin군은 태아곤란증이 2예(1.7%), 이완성 자궁출혈이 5예(4.1%)였다. 5) 경구 prostaglandin E2정의 투여중 혈압, 맥박, 체온의 현저한 변화나 자궁의 과도한 수축은 관찰할 수 없었다. 6) 신생아 Apgars score는 prostaglandin E2군의 평균치는 1분에 9.10, 5분에 9.59였고, oxytocin군의 경우 평균치는 1분에 9.18, 5분에 9.94였다. 이상의 결과로 보아 prostaglandin E2정의 경구투여에 의한 유도분만방법이 안전하고 효과적인 방법이라고 사료되는 바이다. This study is a clinical analysis of comparative study between 42 cases induced labor by oral prostaglandin E2 and 120 cases induced labor by continuous intravenous oxytocin infusion who were admitted to the department of OB. & GYN. of Severance Hospital, School of Medicine, Yonsei University, from March 1978 to August 1978. The pelvic score for inducibility was determined by modified Bishops score, and they were divided into three categories "below 4" "5-9" and "above 10". The results of study were as follows: 1. Successful induction "below 4" by modified Bishops score was 59.1% in prostaglandin E2 group and 55.8% in oxytocin group, and that in score of "5-9", 100% in prostaglandin E2 group, 91.3% in oxytocin group, and that in score of "above 10" 100% in both groups. 2. Mean induction-delivery time in prostaglandin E2 group, primipara was 12.78 3.8 hours and multipara was 5.26 3.22 hours and that in oxytocin group, primipara was 12.47 1.9 hours and multipara was 3.76 0.55 hours. 3. Mean total dosage of prostaglandin E2 was 2.46 0.4mg for induction delivery. 4. Side effects in prostaglandin E2 group consists of nausea and vomiting(9.5%), diarrhea(2.4%), and atonic bleeding(4.7%), and that in oxytocin group consists of fetal distress(1.7%) and atonic bleeding(4.1%). 5. No significant changes were noted in blood pressures, pulse rate and body temperature, and nocase of uterine hypertonicity was observed.

단순균형전좌 46,XY, t(13p;17p) 태아의 산전진단 1 예

김세광(SK Kim),김인규(IK Kim),김미순(MS Kim),이명선(MS Lee) 대한산부인과학회 1989 Obstetrics & Gynecology Science Vol.32 No.11

분만력이 매우 불량하였던 산모에서 단순균형전좌 46,XY, t(13p;17p) 보인자임을 확인한 후 적절한 유전상담을 시행하였다. 양수천자에 의해 태아에서도 동일한 단순균형전좌가 잇음을 산전진단하엿으며 임신 40주에 정상 표현형의 영아를 분만시켰기에 간단히 문헌고찰과 함께 보고하는 바이다. A 27-year-old woman wa referred for genetic counseling because she had experinced three miscarriages and one live-born multiple anomalous baby. We karyotyped both partners. The mother was found to be a carrier of a simple balanced translocation . the formal karyotpye wa 46,XY, t(13p;17p) . Amniocentesis was performed at the 17th week of gestation . The fetus also was found to be a carrier of the identical translocation . A phenotypically normal male infant was delivery at the 40th week of gestation.

임산부 말초혈액에서 중합효소연쇄반은 ( PCR ) 을 이용한 태아의 성염색체 분석과 이의 산전유전 진단응용

송찬호(CH Song),양영호(YH Yang),김인규(IK Kim),김동욱(DW Kim),김미순(MS Kim),유향숙(HS Yoo),이미화(MH Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.3

산전유전검사를 받을 임산부 22예를 대상으로 이들의 말초혈액을 채취하여 Y chromosome-specific ZFY gene DNA sequence와 Y chromosome 단완의 DYS 14 locus에 위치한 Y-specific sequence를 nested polymerase chain reaction assay법으로 증폭하여 산전 태아 성(fetal sex)판정을 시도하여 다음과 같은 결과를 얻었다. 1. ZFY 유전자의 primer인 Z1, Z2 및 Z3, Z4를 이용한 중합효소연쇄반응 결과, 여아 및 남아를 임신한 전예에서 양성띠가 나타나 비특이성을 보였다. 2. Y-chromosome DYS 14 locus의 sequence primer인 Y1.5, Y1.6 및 Y1.7, Y1.8 primer를 이용한 중합효소연쇄반응 결과, sensitivity는 76.9%, specificity는 55.5%였으며, positive 및 negative predictive value는 각각 71.4%와 62.5%였다. 이를 임신주수별로 분석하여 보면 임신 초기, 중기 및 말기의 positive predictive value는 각각 66.6%, 66.6%와 80%로, negative predictive value는 각각 50%, 50% 및 100%로 나타났으며, 임신 9-16주에는 여아를 임신한 임산부 중 남성 특이의 band가 나타나는 경우가 6예중 3예, 남아를 임신한 임산부 중 남성특이의 band가 나타나지 않는 경우가 7예중 3예로 낮은 신회도를 보였으나 임신 18-40주에는 남아인 경우 1예를 제외하고는 남성 특이 band가 나타났으며, 여아인 경우는 모든 예에서 198 base pair의 남성 특이 band가 나타나지 않았다. 저자들은 본 연구에서 모체 말초혈액에서 중합효소연쇄반응(PCR)을 이용한 태아의 성판정은 임신후기에는 가능하나 임신초기에 있어서는 그 신뢰도가 낮은 것으로 생각 된다. 따라서, 임신 초기 모체혈액내에 있는 태아세포만을 선별적으로 구별할 수 있는 방법을 이용하여 Y1.5, Y1.6 및 Y1.7, Y1.8 primer를 이용 PCR을 하면 정확한 태아의 성판정이 가능할 것으로 사료된다. 본 연구는 연세대학교 의과대학 교수연구비에 의해서 이루어짐 (1994년도). Objectives : Detection of Y-chromosome specific gene in the maternal circulation has clinical importance because of its potential usefulness in determining fetal sex in mothers with severe X-linked disorders such as classic hemophilia A and Duchenne`s muscular dystrophy. Numerous attempts have been made to identify Y specific gene in bloods of mothers bearing male fetuses, however, the results have been controversial. Therefore, we have investigated the use of a nested polymerase chain reaction assay for the detection of a fetal specific Y-chromosome sequence. Methods : Y chromosome specific ZFY gene DNA sequence(using Z1, Z2 and Z3, Z4 primers) and Y chromosome sequence in DYS 14 locus (using Y1.5, Y1.6 and Y1.7, Y1.8 primers) have been identified by an in vitro enzymatic deoxyribonucleic acid amplification method in peripheral blood specimens of 22 pregnant women with gestational ages of 9 to 40 weeks. Results : All women bearing male or female baby were positive for the ZFY gene. Thirteen fetuses were confirmed as males by amniocentesis or chorionic villi sampling, and 10 of these were positive for the Y chromosome specific sequence in DYS 14 locus using Y1.5, Y1.6 and Y1.7, Y1.8 primers(sensitivity 76.9%), however, 4 of the 9 cases diagnosed as females were also positive(specificity 55.5%). Positive and negative predictive values were 71.4% and 62.5%. In terms of the gestational age, positive predictive values of 66.6%, 66.6% and 80% were obtained for the first, second and third trimesters, respectively. The corresponding negative predictive values are 50%, 50%, and 100%, respectively. Conclusion : Fetal sex determination by PCR employing maternal peripheral blood is usually possible in late pregnancy. It is less reliable in early pregnancy. It appears that using a method separating fetal cells from maternal blood and then by running PCR on these cells with Y1.5, Y1.6 and Y1.7, Y1.8 primers could make a fairly accurate fetal sex determination.

태아 심에코로 진단한 심실중격결손이 없는 대혈관 전위 2 례

김인규,조진호,김경률,김병성,이경술,서동만 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.9

Transposition of the great arteries with intact ventricular septum (TGA IVS) is a cyanotic congenital heart disease with high neonatal mortality without early diagnosis. But TGA IVS is known to have good prognosis if treated by arterial switch operation (ASO) within 2 weeks after birth with early diagnosis. We diagnosed two cases of TGA IVS prenatally by fetal echocardiography. A case was diagnosed at 26th weeks of gestation, and the mother was transferred to a cardiac center for planned delivery. The baby had received ASO on postpartum 7th day, but he died of right ventricular failure on postoperative 8th day. The second case was diagnosed at 37th gestational weeks and was transferred to Asan medical center immediately after birth. And he is doing well without any treatment after ASO.

약 , 환경과 선천성기형 관계에 관한 연구

김인규,조주연,이규형 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.10

차병원 산부인과에서 1992년 11월부터 1993년 12월까지 분만한 모든 산모 7025예에 대하여 태아기형유발가능성 이있다고 추정되는 약물이나 환경 등에 노출여부에 대하여 분만전에 설 문지를 작성하고 기형아 출산여부를 조사하는 후향적 연구를 하였다. 기형아를 분만하지 않 은 군은 정상아군으로 기형아를 출산한 군은 기형아군으로하여 비교하였는데 결과는 다음과 같다. 1. 6706예는 기형이 없는 아이를 분만하였고 319예는 기형아를 분만하여 4.5%의 기형아 빈 도를 보여주었다. 정상아군은 2.5% 기형아군은 4.4%가 과거에 기형아를 분만한 경험이 있었다. 2. 두군간에 나이에 따른 차이는 없었으나 35세이상이 되면 35세 이전에 비하여 기형아 출산이 증가하는 것으로 나타났다. 자연 유산경력과 기형아 출산과는 관계가 없는 것으로 나타났다. 3. 1/3이 약간 넘는 산모가 직업을 가지고 있었고 직업의 유무는 두 군간에 차이가 없었으나 교사는 정상아군에서 많은 것으로 나왔다. 4. 약물이나 유해할 가능성이 있는 환경에 노출되는 빈도는 두 군 모두 50%를 약간 넘었다. 방사선에 노출되거나 사용하는 비율이 약 30%가 되었다. 임신 초기에 방사선, 약물, 유해 가스 또는 술이나 담배에 노출된 산모중 두군 모두 약 1/4은 임신여부를 모르고 노출된 사람이었다. 5. 임신중 커피를 마신 산모는 72%, 술을 마신산모는 4.9% 담배를 피운 산모는 1.2%로 나 타났으며 두군간에 유의한 차이는 없었다. 임신 1기에 커피를 마시는 산모는 정상아군이 39.4%, 기형아군이 39.2%였고 술을 마신 산모는 정상아군이 3.2%, 기형아군이 2.2%였으며 담배를 피운 산모는 정상아군이 0.8%, 기형아군이 0.9%로 비슷하게 나타났으며 역시 두군간 에 유의한 차이는 없었다. 6. 임신 15-20주 사이에 시행한 산모 혈청 alpha-feto protein검사결과 정상아군 1.08+-0.38MOM이었고 ,기형아군 1.21+-0.50MOM으로 유의한 차이는 없었다. 0.5MOM미만 되 는 경우와 2.0-2.4MOM 및 2.5이상 되는 예는 기형아군이 정상아군보다 유의하게 많았다. 7. 선천성 기형 빈도가 높은 기관으로는 귀의 이상을 포함한 피부가 66예로 0.9% 심장 혈관 계가 59예로 0.8%, 비뇨 생식기계가 49예로 0.7%, 골격계가 46예로 0.7% 그리고 소화기계가 24예 7.5%였다. 이러한 기관이나 복합 기형의 경우 직업, 약사용, 기호품 사용 등 상당히 많 은 산모가 노출되는 관점에 대하여 빈도를 비교해보았으나 해당되는 정상아군에 비하여 유의한 차이가 없었다. A study was undertaken by questionaire to 7025 mothers who delivered at Cha General Hospital from NOV. 1992 to Dec. 1993 considering their exposure to drug, envionment or other potential teratogenic substances. Those who delivered their babies without amy malformations were classified as the control group . and those with the malfomations as the study group . The results were as follows. 1. 6706 cases delivered their babies without any malfomation and 319 cases (4.5%) with malfomations. 2. There were no significant age difference in both groups, but the incidence of delivering malformed childeren were higher in mothers above 34 years. 3. About 1/3 of the of paturients were working mothers. There were no significant differences according to occupational bases, but there was a tendency of more teachers in the control group . 4. About 50% of mothers in both group were exposed to drugs or other potentially hazadous substances. Those of about 30 % were exposed to radiation or drug. About 1/4 of mothers in both group who were exposed to radiation, drug, noxious gas, alchohol or tobacco in first trimester were not aware of their pregnancy. 5. 72% of total mother drank coffee 4.9% alchohol, 1.2 % tobacco and there is no significant difference between two groups. 39.4% of control group and 39.2% of study group drank coffee in the first trimester, 3.2 and 2.2% alchohol, 0.8 and 0.9% tobacco respectively but there was no significant difference. 6. a-feto protein value was measured to be 1.08+-0.38 MOM(multiple of the median for the population) for the control group and 1.21+-0.50 MOM for the study group which was not significantly different. The study group had more motheres with a-feto protein value below 0.5MOM, 2.0-2.4MOM and over 2.4MOM than control group . 7. The organs involved in congenital malformation were skin including car in 66 cases (0.9%), cardiovascular system 59 cases (0.8%), urogenital system was cases(0.7%), skeletal system 46 cases (0.7%) and degestive system was 24 cases(7.5%), considering the congenital malformation involving these organs and complex abnomalities, there was no significant difference between both groups, whether they were working mothers drug users, drinkers or tobacco smokers.

Noonan증후군 1 례

김인규,이숙환,곽인평,윤태기,차광열,남윤성 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.4

저자들은 불임환자에서 Turner증후군의 징후를 보이고 정상핵형을 가진 Noonan증후군 1 례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Noonan syndrome is featured by short stature, mental retardation, hypertelorism, epicanthal folds, dental malocclusion, pectus excavatum and congenital heart disease[mainly ventricular septal defects and pulmonary stenosis]. The phenotype has some similarities with Turner syndrome, but the karyotype is normal and males can be affected. Noonan syndrome is mostly sporadic, but an autosomal dominant transmission has been occasionally documented. The intrauterine sonographic findings have been described in a handful of cases. The most relevant sign is cystic hygroma colli, usually quite small and bilateral. The sign is atypical however, and it is probably shared by all conditions that are associated at birth with webbed neck. A high index of suspicion for Noonan syndrome is suggested when a male fetus or a female fetus with normal chromosome is found to have small bilateral cervical hygromas in association with congenital heart disease. We have experienced a case of Noonan syndrome in infertile patient with primary amenorrhea. So we report this case with a brief review of literatures.

인공 고관절전치환술에 있어서 경막외마취와 전신마취의 비교연구

김완식,김교상,박동호,전세웅,서정국,김인규,김경헌,승익상 대한마취과학회 1987 Korean Journal of Anesthesiology Vol.20 No.2

Twenty-six casea of general anesthesia and eighteen cases of epidural anesthesia for total his replacement which were performed at department of anestheaiology, Hanrang University Hospital from Jan. 1984 to fun. 1986 were measured blood toss, operation time, volume of whole blood tranafusion and mean arterial blood pressure perioperatively. The result were as follws : 1) Both groups were statistically comparable with regard to sex, height and weight but age of patients were statistically greater in epidural group(p$lt;0.75). The oldest case was 85 years Old in epidural group. 2) The mean operativeblood loss of patients who had their operations under epidural anesthesia was significantly less that that of patients under general anesthesia, being 1,444±769 ml for the epldural group and 2,081±1,051 ml for the general group(p$lt;0.75). 3) The mean bleeding rate of the patients under epidural anesthesia was significantly less that of patients under general Anesthesia, being 9.2±3.0 ml/min for the epidural group and 12.6±5.5 ml/min for the general group(P$lt;0.725). 4) The mean volume of whole blood transfusion of patients under epidural anesthesia was significantly less than that of patients under general aneathesia, being 1,178±854 ml for the epidural group and 1,763±73f ml for the general group(7$lt;0.05). 5) There was no case of deep vein thrombosis both groups.

FISH (Fluorescence in situ hybridization) 을 이용한 신속한 산전 염색체 이수성 (Aneuploidies) 진단

김진영,양영호,김인규,김미순,최은경 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.5

저자들은 산전 염색체검사에 있어서 FISH법의 임상적 유용성을 검증하고자 융모막 융모세포 및 양수세포, 제대혈 검사를 통해 얻은 태아 혈액세포를 이용하여 4개의 서로 다른 소식자를 적용, 세포분열 간기 및 중기의 태아 세포에서 염색체 이수성 검사를 실시해 본 결과 총 15예 전체에서 전통적인 세포 염색체 핵형 검사와 일치하는 고무적인 결과를 얻었으며 비록 이번 연구 결과가 증례수가 적어 그 유용성을 검증하기 위해서는 대규모의 전향성 연구가 필요할 것으로 보이나 앞으로 FISH법은 태아 염색체 이수성의 산전 진단에 있어서 신속하고 효과적인 보조적 수단으로 각광받을 것으로 보인다. Introduction: The traditional cytogenetic analysis requires relatively long cell culture time, intensive labour and trained personnel. But in clinical situations, the prenatal diagnosis of genetic disease and incidental finding of abnormal ultrasonographic finding need urgent decisions on future management. So we need more rapid and precise diagnostic tools of prenatal genetic counselling. The fluorescence in situ hybridization (FISH) has been studied for detecting chromosomal aneuploidies because this method can get rapid results of cytogenetic studies. Objectives: To evaluate the clinical utility of prenatal diagnosis of chromosomal aneuploidies by using FISH. Materials and methods: chorionic villi (n=6), amniotic fluid (n=7), fetal blood (n=2) were obtained from 15 pregnancies undergoing fetal karyotyping at 9 to 30 weeks of gestation for prenatal genetic counselling.Karyotyping was performed by both traditional cytogenetics and FISH, using commertially available kits. After the procedures, the results of FISH were compared with the results of traditional cytogenetic studies. Results: In a blind series of 15 samples all, including one case of trisomy 21, one case of trisomy 18 and one case of monosomy X, were correctly identified. Conclusions: FISH is a rapid and effective methods for detection of chromosomal aneuploidies in prenatal diagnosis and yields possible clue of fetal genetic diagnosis with pregnant maternal peripheral blood.

임신중기 원인불명 모체혈청 알파태아단백치 상승 산모의 주산기 예후

송찬호,양영호,김세광,김인규,박용원,조재성,김지수,김행수 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.1

임신 15주에서 20주사이에 MSAFP치가 2.5 MoM이상을 보인 산모중 재태연령이 정확히 확 인되고 초음파검사상 다태아, 태아 사망, 태아 선천성기형 등이 발견되지 않았던 원인불명 MSAFP 상승 산모군과 MSAFP가 0.25MoM과 2.5MoM 사이의 정상대조군 산모사이의 주산기 예후를 비교분석하였다. 전체 1,731명의 산모중 원인불명 MSAFP 상승산모는 35명으로 2.0%의 발생빈도를 보였다. 이들 원인불명 MSAFP 상승 산모중 21명에서 양수천자를 시행받았으며 모두 정상 핵형 소 견을 보였다. 이들 원인불명 MSAFP 상승 산모군에서 정상 대조군 산모에 비해 태아의 선 천성기형(6.9% versus 1.0% ; P$lt;.05) 과 태아사망 (13.8% versus 0.4% ; P$lt;.001)의 발생빈도 는 유의하게 높았으나 조산, 자궁내 태아발육지연, 저체중아 및 임신성 고혈압 등의 발생빈도는 2군간에 유의한 차이가 없었다. 결론적으로 임신중기 원인불명 MSAFP 상승시 태아기 형 및 태아사망 발생위험이 증가됨을 산모에게 주지시켜 주는 것이 중요하며 이들은 분만시 까지 태아안녕 평가검사 등으로 철저한 추적관찰이 필요하다고 사료된다. We conducted this sutdy to investigate whether patients with unexplained midtrimester elevation of maternal serum alpha-fetoproten (MSAFP) are at increased risk for adverse perinatal outcomes. The inclusion criteria for patients with unexplained MSAFP elevations were a MSAFP level 2.5 or greater multiples of median (MoM), a single gestation, a confirmed gestional age, and no fetal malformation or death on ultrasonography. Patients with MSAFP levels 0.25 to $lt; 2.5 MoM served as controls. Maternal blood as drawn at 15-20 weeks estimated gestional age. Of the 1,731 patients screened, 35(2.0%) had an unexplained elevated MSAFP level. 21 of 29 patients with unexplained MSAFP elevations accepted genetic amniocentesis and the fetal karyotypes were normal in all cases. Patients with unexplained MSAFP levels had significantly higher incidence of fetal congenital malformation (6.9% versus 1.0% ; P$lt;.05) and fetal death (13.8% versus 0.4% ; P$lt;.001) than those with normal MSAFP. But no significant differences were observed in the incidence of preterm delivery, intrauterine growth retardation, low birth weight, and pregnancy-induced hypertension. This study suggests that patients with unexplained midtrimester elevations of MSAFP are incresed risk for fetal congenital malformation and fetal death. Careful clinical follow-up elevations is warranted in these patients.

임신 중기 산모혈청 삼중 표지자를 이용한 다운증후군 태아의 선별검사 결과 위양성 산모의 임신 예후

송찬호,양영호,김재욱,김세광,김인규,조재성,김석영,최형민,임종철 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.3

Objective: Our purpose was to study the pregnancy outcome in women whose triple marker screening [maternal serum AFP, unconjugated estriol, hCG, and maternal age] indicating an increased risk for Down syndrome [more than 1 : 270] was not confirmed by amniocentesis [false-positive result]. Methods: Between January 1995 and August 1997, 1,070 pregnant women undergoing second trimester triple marker screening for Down syndrome who gave birth at our institution were evaluated. The pregnancy outcomes of 56 women with false-positive screens for Down syndrome were compared with 1,014 screen negative controls. The pregnancy outcomes were obtained from hospital delivery records. Pregnancies with fetal chromosomal and structural anomalies were excluded from the study Results: An adverse pregnancy outcome occurred in 6 of 56 women [10.7%] with false-positive screens for Down syndrome, compared with 80 of 1,014[7.9%] in the screen negative controls [p=0.291]. The study group was not significantly different from the control group in the incidence of preterm delivery [5.4% vs. 3.5%], preeclampsia [0% vs. 1.8%], abruptio placentae [0% vs. 0.2%], intrauterine growth retardation [5.4% vs. 2.0%], and fetal death [0% vs. 0.5%]. Among six women with adverse pregnancy outcome in the study group, low uE3 level[≤ 0.75 MoM] and high hCG level [≥ 2.0 MoM] were more frequently associated with adverse pregnancy outcome than low AFP level[≤ 0.4 MoM]. Conclusion: Women with false-positive screens for Down syndrome do not appear to be associated with adverse pregnancy outcomes.